The present invention relates to a method for rapid parallel detection of one or more analytes in a plurality of samples. In particular, the invention relates to a method for parallel detection of one or more non-volatile analytes in a plurality of samples, at least one of which comprises a volatile component.
Combinatorial techniques are being extended to diverse areas of chemical research. For example, combinatorial techniques can be used to identify and optimize catalysts and reaction conditions for polymerization reactions. However, the complexity of these reaction mixtures often complicates the quantitation of individual reactants, products, side-products or intermediates. In the synthesis of polycarbonates, current analytical measurements of the reactant bisphenol A (BPA) involve traditional separation techniques that are too time consuming where a large number of samples are involved (see, for example, J. E. Biles, T. P. McNeal, T. H. Begley and H. C. Hollifield, Journal of Agricultural Food Chemistry, volume 45, pages 3541-3544 (1997)).
Use of spectroscopic imaging can lead to increased sample throughput. With parallel spectroscopic imaging of large sample arrays, the measurement time is nearly independent of the number of samples. This advantage makes possible rapid analysis of even highly dense combinatorial arrays. U.S. Pat. No. 5,854,684 to Stabile et al. describes techniques for imaging sample arrays by a variety of spectroscopic techniques. However, the techniques described in this reference are unsuitable for determination of an analyte when other reaction components interfere with that determination.
Parallel fluorescence imaging provides low detection limits on variety of species that have native fluorescence. Unfortunately, the low fluorescence quantum yields of many analytes of interest, including BPA, preclude their direct detection. In addition, possible interferences from other reaction components (e.g., phenol) complicate reliable quantitation.
Polarity sensitive reagents (e.g., solvatochromic dyes) have been used for detection of volatile components and solvents of differing polarity. For example, a polarity sensitive reagent has been immobilized onto an analyte-permeable membrane to form a sensor (see, for example, S. M. Barnard and D. R. Walt, Environmental Science and Technology, volume 25, pages 1301-1304 (1991); and R. A. Potyrailo and G. M. Hieftje, Fresenius"" Journal of Analytical Chemistry, volume 364, pages 32-40 (1999)). A known limitation of this detection approach is the low selectivity of measurements in complex multi-component solutions or gas mixtures. This limitation can be addressed by using an array of sensors with diverse intrinsic polarities (see, for example, T. A. Dickinson, J. White, J. S. Kauer and D. R. Walt, Nature, volume 382, pages 697-700 (1996); and T. A. Dickinson, D. R. Walt, J. White and J. S. Kauer, Analytical Chemistry, volume 69, pages 3413-3418 (1997)). However, the use of separate sensor array for each of the combinatorial samples significantly complicates the measurement system.
As such, there remains a long felt, yet unappeased need for a method of rapidly determining various properties of poorly fluorescing analytes when dealing with a large number of multi-component samples.
Accordingly, the present invention is directed to a system and method utilizing analyte-modulated fluorescence of a solvatochromic dye on an inert sorbent material. In one embodiment, the method comprises providing a plurality of analytical samples comprising at least one non-volatile analyte for which the concentration is to be determined and at least one volatile component; providing an analytical matrix comprising a plurality of spatially differentiated analytical sites, each site comprising a sorbent material and a solvatochromic dye; delivering a known amount of each analytical sample onto at least one unique analytical site; subjecting the matrix to conditions effective to substantially evaporate the at least one volatile component of the analytical samples; irradiating a plurality of the analytical sites on the matrix with a first selected wavelength range; detecting a spectroscopic characteristic of the solvatochromic dye from each analytical site on the matrix with a second selected wavelength range; and determining a concentration of the non-volatile analyte at each analytical site based on the spectroscopic characteristic of the solvatochromic dye.